| 11. |
- Irungu, Beatrice N., et al.
(author)
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Antiplasmodial and cytotoxic activities of the constituents of Turraea robusta and Turraea nilotica
- 2015
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In: Journal of Ethnopharmacology. - : Elsevier Ireland Ltd. - 0378-8741 .- 1872-7573. ; 174, s. 419-425
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Journal article (peer-reviewed)abstract
- Ethnopharmacological relevance: Turraea robusta and Turraea nilotica are African medicinal plants used for the treatment of a wide variety of diseases, including malaria. The genus Turraea is rich in limonoids and other triterpenoids known to possess various biological activities. Materials and methods: From the stem bark of T. robusta six compounds, and from various parts of T. nilotica eleven compounds were isolated by the use of a combination of chromatographic techniques. The structures of the isolated compounds were elucidated using NMR and MS, whilst the relative configuration of one of the isolated compounds, toonapubesin F, was established by X-ray crystallography. The antiplasmodial activities of the crude extracts and the isolated constituents against the D6 and W2 strains of Plasmodium falciparum were determined using the semiautomated micro dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-3H, where G is guanine) hypoxanthine into the malaria parasite. The cytotoxicity of the crude extracts and their isolated constituents was evaluated against the mammalian cell lines African monkey kidney (vero), mouse breast cancer (4T1) and human larynx carcinoma (HEp2). Results: The extracts showed good to moderate antiplasmodial activities, where the extract of the stem bark of T. robusta was also cytotoxic against the 4T1 and the HEp2 cells (IC50<10 μg/ml). The compounds isolated from these extracts were characterized as limonoids, protolimonoids and phytosterol glucosides. These compounds showed good to moderate activities with the most active one being azadironolide, IC50 2.4±0.03 μM and 1.1±0.01 μM against the D6 and W2 strains of Plasmodium falciparum, respectively; all other compounds possessed IC50 14.4-40.5 μM. None of the compounds showed significant cytotoxicity against vero cells, yet four of them were toxic against the 4T1 and HEp2 cancer cell lines with piscidinol A having IC50 8.0±0.03 and 8.4 ±0.01 μM against the 4T1 and HEp2 cells, respectively. Diacetylation of piscidinol A resulted in reduced cytotoxicity. Conclusion: From the medicinal plants T. robusta and T. nilotica, twelve compounds were isolated and characterized; two of the isolated compounds, namely 11-epi-toonacilin and azadironolide showed good antiplasmodial activity with the highest selectivity indices. © 2015 The Authors. Published by Elsevier Ireland Ltd.
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| 12. |
- Koller-Smith, Louise I. M., et al.
(author)
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Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17
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Journal article (peer-reviewed)abstract
- Background: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of themodels were compared. Results: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and >= 32 weeks, AUC 0.50-0.65; >= 1500 g and >= 32 weeks, AUC 0.60-0.62). Conclusion: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking.
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| 13. |
- Koushik, Anita, et al.
(author)
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Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies.
- 2015
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In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 26:9, s. 1315-27
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Journal article (peer-reviewed)abstract
- PURPOSE: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer.METHODS: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model.RESULTS: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95% confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95% CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types.CONCLUSION: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.
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| 14. |
- Lawrence, M. A. W., et al.
(author)
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Synthesis and Structure of a Novel Substituted Benzothiazolyl-N-phenyl-2-pyridinecarbothioamide; Kinetics of Formation and Electrochemistry of Two of its Palladium Pincer Complexes
- 2015
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In: Australian Journal of Chemistry. - : CSIRO Publishing. - 0004-9425. ; 68:5, s. 731-741
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Journal article (peer-reviewed)abstract
- The synthesis and crystal structures of bis-N-(2,5-dimethoxyphenyl)pyridine-2,6-dicarbothioamide (dicarbothioamide I) and 6-(4,7-dimethoxy-2-benzothiazolyl)-N-(2,5-dimethoxyphenyl)-2-pyridinecar bothioamide (L-1) as well as the syntheses of the palladium(ii) chloride and acetate pincer complexes are reported. The stability constant for the palladium complex formation at 25 degrees C was found to be (2.04 +/- 0.26)x10(4)dm(3)mol(-1) and (2.30 +/- 0.19)x10(4)dm(3)mol(-1) with H-f=8 +/- 1kJmol(-1), S-f=108 +/- 10JK(-1)mol(-1), and H-f=17 +/- 4kJmol(-1) and S-f=140 +/- 20JK(-1)mol(-1) for the PdClL1 and Pd(OAc)L-1, respectively. The kinetics of formation of the palladium(ii) complexes were investigated and the mechanism is proposed to be associative in nature (H-1(double dagger)=34 +/- 2kJmol(-1) and S-1(double dagger)=-113 +/- 8JK(-1)mol(-1), and H-1(double dagger)=37 +/- 3kJmol(-1) and S-1(double dagger)=-100 +/- 8JK(-1)mol(-1) for the PdClL1 and Pd(OAc)L-1 species, respectively). The electrochemical measurements of the acetonitrile solutions revealed irreversible electron transfers consistent with the electrochemical decomposition of the ligand and its coordination complexes.
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| 15. |
- Noresson, A. L., et al.
(author)
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Designing interactions by control of protein-ligand complex conformation : Tuning arginine-arene interaction geometry for enhanced electrostatic protein-ligand interactions
- 2018
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 9:4, s. 1014-1021
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Journal article (peer-reviewed)abstract
- We investigated galectin-3 binding to 3-benzamido-2-O-sulfo-galactoside and -thiodigalactoside ligands using a combination of site-specific mutagenesis, X-ray crystallography, computational approaches, and binding thermodynamics measurements. The results reveal a conformational variability in a surface-exposed arginine (R144) side chain in response to different aromatic C3-substituents of bound galactoside-based ligands. Fluorinated C3-benzamido substituents induced a shift in the side-chain conformation of R144 to allow for an entropically favored electrostatic interaction between its guanidine group and the 2-O-sulfate of the ligand. By contrast, binding of ligands with non-fluorinated substituents did not trigger a conformational change of R144. Hence, a sulfate-arginine electrostatic interaction can be tuned by the choice of ligand C3-benzamido structures to favor specific interaction modes and geometries. These results have important general implications for ligand design, as the proper choice of arginine-aromatic interacting partners opens up for ligand-controlled protein conformation that in turn may be systematically exploited in ligand design.
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| 16. |
- Petimar, J, et al.
(author)
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Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.
- 2019
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:3, s. 468-475
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality.METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures.RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously.CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.
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| 17. |
- Steinhaus, Daniel A, et al.
(author)
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Chocolate intake and incidence of heart failure : Findings from the Cohort of Swedish Men.
- 2017
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 183, s. 18-23
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Journal article (peer-reviewed)abstract
- The objective of this study was to evaluate the association of chocolate consumption and heart failure (HF) in a large population of Swedish men.METHODS: We conducted a prospective cohort study of 31,917 men 45-79 years old with no history of myocardial infarction, diabetes, or HF at baseline who were participants in the population-based Cohort of Swedish Men study. Chocolate consumption was assessed through a self-administrated food frequency questionnaire. Participants were followed for HF hospitalization or mortality from January 1, 1998, to December 31, 2011, using record linkage to the Swedish inpatient and cause-of-death registries.RESULTS: During 14 years of follow-up, 2,157 men were hospitalized (n=1,901) or died from incident HF (n=256). Compared with subjects who reported no chocolate intake, the multivariable-adjusted rate ratio of HF was 0.88 (95% CI 0.78-0.99) for those consuming 1-3 servings per month, 0.83 (95% CI 0.72-0.94) for those consuming 1-2 servings per week, 0.82 (95% CI 0.68-0.99) for those consuming 3-6 servings per week, and 1.10 (95% CI 0.84-1.45) for those consuming ≥1 serving per day (P for quadratic trend=.001).CONCLUSIONS: In this large prospective cohort study, there was a J-shaped relationship between chocolate consumption and HF incidence. Moderate chocolate consumption was associated with a lower rate of HF hospitalization or death, but the protective association was not observed among individuals consuming ≥1 serving per day. Journal Subject Codes: Etiology: Epidemiology, Heart failure: Congestive.
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| 18. |
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| 19. |
- Beltempo, Marc, et al.
(author)
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Respiratory Management of Extremely Preterm Infants : An International Survey
- 2018
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In: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:1, s. 28-36
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Journal article (peer-reviewed)abstract
- BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies.OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration.METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015.RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%).CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.
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| 20. |
- Björn, Camilla, et al.
(author)
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Efficacy and safety profile of the novel antimicrobial peptide PXL150 in a mouse model of infected burn wounds
- 2015
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In: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 45:5, s. 519-524
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Journal article (peer-reviewed)abstract
- The urgent need to develop novel antimicrobial therapies has stimulated interest in antimicrobial peptides as therapeutic candidates for the treatment of infectious diseases. The aim of this study was to evaluate the anti-infectious effect of the synthetic antimicrobial peptide PXL150, formulated in hydroxypropyl cellulose (HPC) gel, on Pseudomonas aeruginosa in vitro and in an in vivo mouse model of infected burn wounds as well as to assess the in vivo safety profile of PXL150 in rats and rabbits. Minimal microbicidal concentration analysis showed prominent efficacy of PXL150 against P. aeruginosa in vitro, which was further enhanced in formulating the peptide in HPC gel. Application of 1.25, 2.5, 5, 10 and 20 mg/g PXL150 in HPC gel twice daily for four consecutive days significantly reduced bacterial counts in the burn wounds compared with non-treated or placebo-treated controls. Continuous bioluminescence measurements of the bacteria revealed a pronounced anti-infective effect already at the first day post infection by PXL150 in concentrations of >= 2.5 mg/g. In the non-clinical safety studies, PXL150 showed a favourable safety profile following repeated administration systemically and locally in rats and rabbits, respectively. In conclusion, these data support that PXL150 has the potential to be an effective and safe drug candidate for the treatment of infected burn wounds. The findings encourage the progression of PXL150 as a novel topical treatment of microbial infections.
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